Effect of vinconate, an indolonaphthyridine derivative, on dopamine and serotonin concentrations in dialysate from the striatum of freely moving rats: brain microdialysis studies

The effect of (+/-)-methyl 3-ethyl-2,3,3a, 4-tetrahydro-1H-indolo[3,2,1-de][1,5]naphthyridine -6-carboxylate monohydrochloride (vinconate), an indolonaphthyridine derivative, on dopamine and serotonin concentrations in dialysate from the striatum of freely moving rats was examined by brain microdialysis. Twenty-minute samples collected were used to determine dopamine and serotonin by high-performance liquid chromatography in a single run. The basal extracellular levels of dopamine and serotonin were 41.12 +/- 5.04 and 10.41 +/- 1.71 (fmol/20 min), respectively. Dopamine concentrations in dialysate were significantly increased after a single treatment with vinconate (50-200 mg/kg p.o.). Tetrodotoxin (10 microM) added into the dialysis perfusate decreased dopamine concentrations in dialysate and vinconate had no effect on dopamine concentrations in dialysate when administered after tetrodotoxin. The vinconate-induced increase in dialysate dopamine concentrations was significantly reduced by scopolamine (1 microM) and N0434 (1 microM), respectively. Moreover, daily treatment with vinconate (25 mg/kg p.o.) for 7 days resulted in enhanced dopamine and serotonin concentrations in dialysate induced by subsequent vinconate treatment. These findings suggest that vinconate administered systemically can enhance dialysate dopamine concentrations and this effect may be related to the muscarinic receptor and the dopamine D2 receptor. The present findings also suggest that repeated treatment with vinconate may augment these effects of vinconate on dopamine and serotonin concentrations in dialysate from the brain.